Another disappointing HDL therapy?

News - July 1, 2013

The ASSURE-trial, a phase IIb trial evaluating RVX-208 in high-risk cardiovascular patients with low high-density lipoprotein (HDL), did not meet its primary endpoint of a -0.6% change in percent atheroma volume as determined by intravascular ultrasound (IVUS).
RVX-208 (Resverlogix) is a first-in-class orally active BET-protein inhibitor that removes atherosclerotic plaque via reverse cholesterol transport by increasing the levels of ApoA-I, a key component of the HDL particles required for reverse cholesterol transport.
ASSURE was a phase 2b multicenter, double-blind, randomized, parallel group, placebo-controlled trial studying RVX-208 in 324 patients with coronary artery disease and low HDL levels. After 26 weeks, those who received RVX-208 displayed a 0.4 percent reduction in percent atheroma volume as determined by intravascular ultrasound (p= 0.08).
The secondary endpoints of regression of total coronary atheroma volume and increases in apolipoprotein A-I (ApoA-I) and HDL cholesterol levels were met.
The placebo results were stronger than expected, which requires further exploration.
This is the next in a series of disappointments that occurred in the area of HDL-raising therapies (niacin, CETP-inhibitors). RVX-208 was intended to not just raise HDL levels, but to enhance the functional aspect of HDL.
A remaining question is whether a 26 week study with an IVUS endpoint was capable of measuring the potential clinical benefits of the drug; IVUS has never been validated as a surrogate endpoint.
The full data set will be analysed over the coming weeks and months to determine whether continued development of RVX-208 in cardiovascular disease is warranted.